-Derived Extracellular Vesicles Enhance Oral Squamous Cell Carcinoma Malignancy Through BRCA1/EXO1/TP53BP1 Modulation.

BACKGROUND

Oral squamous cell carcinoma (OSCC) is a common malignancy among Asian populations, and emerging evidence suggests that oral microbiota dysbiosis may play a role in its pathogenesis. This study investigates the role of the oral microbiome, particularly (), in OSCC progression and explores the underlying molecular mechanisms involving bacterial extracellular vesicles (EVs).

METHODS

16S rRNA sequencing was conducted on tumor and adjacent non-tumor tissues from OSCC patients to identify microbial composition. In vitro and in vivo experiments were used to evaluate the effects of on OSCC proliferation and cell cycle progression. GW4869, an inhibitor of EVs' release, was applied to validate the EVs-mediated mechanisms. Extracellular vesicles from (SBL-EVs) were isolated using ultracentrifugation and characterized by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). High-throughput sequencing and functional assays were performed to identify signaling pathways regulated by SBL-EVs.

RESULTS

Tumor tissues exhibited a significant enrichment of compared to non-tumor tissues. promoted OSCC proliferation and cell cycle progression both in vitro and in vivo, which was reversed by GW4869 treatment. SBL-EVs were successfully isolated and characterized, and they were found to promote OSCC progression by activating the BRCA1/EXO1/TP53BP1 signaling axis.

CONCLUSION

This study demonstrates the oncogenic role of in OSCC, mediated through EVs-dependent regulation of the BRCA1/EXO1/TP53BP1 pathway. Targeting bacterial EVs or their downstream signaling may represent a novel therapeutic strategy for OSCC.